Biomedical subjects

G Bernardi

Publications and source records attributed to G Bernardi.

At least 19 recordsLinked to original sources

PubMed2006

Upper motor neuron involvement in X-linked recessive bulbospinal muscular atrophy.

OBJECTIVE: Clinicopathological findings of X-linked recessive bulbospinal muscular atrophy (SBMA) are indicative of lower motor neuron and primary sensory neuron involvement. The aim of our study was to investigate the presence of subclinical upper motor neuron (UMN) dysfunction in this disease. METHODS: Two siblings with clinical presentation, routine electrophysiological tests, histopathological features of muscle and nerve biopsies and genetic testing consistent with diagnosis of SBMA underwent transcranial magnetic stimulation (TMS). The analysed parameters were motor evoked potential (MEP) threshold, silent period (SP) and central motor conduction time. Intracortical inhibition with paired pulses from 1 to 6ms interstimulus intervals (ISIs) was evaluated in the older brother. RESULTS: MEP parameters were significantly altered in limb and cranial muscles and MEP suppression after paired stimulation significantly reduced in the older brother. MEP abnormalities were present in one lower limb, but SP abolished in all limbs, in the younger brother. CONCLUSIONS: Subclinical involvement of UMNs may be present in patients affected by SBMA. This finding suggests that the array of neuronal systems whose function may be affected by the pathogenic process of SBMA is larger than it was considered so far. SIGNIFICANCE: TMS is a sensitive diagnostic tool for the identification of UMN dysfunction and should be included in the diagnostic evaluation of patients with SBMA.

Aged↗

PubMed2006

Search for pair production of scalar bottom quarks in pp collisions at square root of s = 1.96 TeV.

A search for direct production of scalar bottom quarks (b) is performed with 310 pb(-1) of data collected by the D0 experiment in pp collisions at square root s = 1.96 TeV at the Fermilab Tevatron Collider. The topology analyzed consists of two b jets and an imbalance in transverse momentum due to undetected neutralinos (chi(1)0), with chi(1)0 assumed to be the lightest supersymmetric particle. We find the data consistent with standard model expectations, and set a 95% C.L. exclusion domain in the (m(b), m(chi(1)0)) mass plane, improving significantly upon the results from run I of the Tevatron.

Journal Article↗

PubMed2006

Search for neutral, long-lived particles decaying into two muons in pp[over] collisions at sqrt[s]=1.96 TeV.

We present a search for a neutral particle, pair produced in pp[over] collisions at sqrt[s]=1.96 TeV, which decays into two muons and lives long enough to travel at least 5 cm before decaying. The analysis uses approximately 380 pb(-1) of data recorded with the D0 detector. The background is estimated to be about one event. No candidates are observed, and limits are set on the pair-production cross section times branching fraction into dimuons + X for such particles. For a mass of 10 GeV and lifetime of 4x10(-11) s, we exclude values greater than 0.14 pb (95% C.L.). These results are used to limit the interpretation of NuTeV's excess of dimuon events.

Journal Article↗

PubMed2006

Search for the standard model Higgs Boson in the pp[over]-->ZH-->nunu[over]bb[over] channel.

We report a search for the standard model (SM) Higgs boson based on data collected by the D0 experiment at the Fermilab Tevatron Collider, corresponding to an integrated luminosity of 260 pb(-1). We study events with missing transverse energy and two acoplanar b jets, which provide sensitivity to the ZH production cross section in the nunu[over]bb[over] channel, and to WH production when the lepton from the W-->lnu decay is undetected. The data are consistent with the SM background expectation, and we set 95% C.L. upper limits on sigma(pp[over]-->ZH/WH)xB(H-->bb[over]) from 3.4/8.3 to 2.5/6.3 pb, for Higgs-boson masses between 105 and 135 GeV.

Journal Article↗

PubMed2006

Search for associated higgs boson production WH-->WWW*-->l+/-nul'+/-nu'+X in pp collisions at square root s=1.96 Te V.

We present a search for associated Higgs boson production in the process pp-->WH-->WWW*-->l;+/-nul'+/-nu'+X in final states containing two like-sign isolated electrons or muons (e+/-e;+/-, e+/-micro+/-, or micro+/-micro+/-). The search is based on D0 run II data samples corresponding to integrated luminosities of 360-380 pb-1. No excess is observed over the predicted standard model background. We set 95% C.L. upper limits on sigma(pp-->WH)xBr(H-->WW*) between 3.2 and 2.8 pb for Higgs boson masses from 115 to 175 GeV.

Journal Article↗

PubMed2006

Search for neutral Higgs bosons decaying to tau pairs in pp[over ] collisions at sqrt[s]=1.96 TeV.

A search for the production of neutral Higgs bosons Phi decaying into tau(+)tau(-) final states in pp[over ] collisions at a center-of-mass energy of 1.96 TeV is presented. The data, corresponding to an integrated luminosity of approximately 325 pb(-1), were collected by the D0 experiment at the Fermilab Tevatron Collider. Since no excess compared to the expectation from standard model processes is found, limits on the production cross section times branching ratio are set. The results are combined with those obtained from the D0 search for Phib(b[over ])-->bb[over ]b(b[over ]) and are interpreted in the minimal supersymmetric standard model.

Journal Article↗

PubMed2006

Search for resonant second generation slepton production at the Fermilab Tevatron.

We present a search for supersymmetry in the R-parity violating resonant production and decay of smuons and muon sneutrinos in the channels mu-->chi(1)(0)mu, mu-->chi(2,3,4)(0)mu, and nu(mu)-->chi(1,2)(+/-)mu. We analyzed 0.38 fb(-1) of integrated luminosity collected between April 2002 and August 2004 with the D0 detector at the Fermilab Tevatron Collider. The observed number of events is in agreement with the standard model expectation, and we calculate 95% C.L. limits on the slepton production cross section times branching fraction to gaugino plus muon, as a function of slepton and gaugino masses. In the framework of minimal supergravity, we set limits on the coupling parameter lambda(211)('), extending significantly previous results obtained in Run I of the Tevatron and at the CERN LEP collider.

Journal Article↗

PubMed2006

Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystonia.

Early-onset torsion dystonia (DYT1) is an autosomal dominant disease caused by a deletion in the gene encoding the protein torsinA. Recently, a transgenic mouse model of DYT1 has been described, expressing either the human wild-type torsinA (hWT) or mutant torsinA (hMT). We recorded the activity of striatal cholinergic interneurons of hWT, hMT, and control mice. In slice preparations, no significant differences were observed in resting membrane potential (RMP), firing activity, action potential duration or Ih current. Quinpirole, a D2-like dopamine receptor agonist, did not produce detectable effects on RMP of cholinergic interneurons in control mice and hWT mice, but in the hMT mice caused membrane depolarization and an increase in the firing rate. D2 receptor activation inhibits N-type high-voltage-activated calcium currents. We found that, in isolated interneurons from hMT mice, the quinpirole-mediated inhibition of N-type currents was significantly larger than in hWT and controls. Moreover, the N-type component was significantly over-represented in hMT mice. The altered sensitivity of N-type channels in hMT mice could account for the paradoxical excitatory effect of D2 stimulation. Our data support the existence of an imbalance between striatal dopaminergic and cholinergic signaling in DYT1 dystonia.

Acetylcholine↗

PubMed2006

Deficits of glutamate transmission in the striatum of experimental hemiballism.

Hemiballism (HB) is a quite rare disorder, generally secondary to stroke, neoplasms or demyelinating plaques, classically considered as almost pathognomonic of a lesion in the subthalamic nucleus (STN). This alteration causes involuntary movements in the chorea-ballism spectrum. One theory is that the output nuclei of the basal ganglia are overinhibited in HB, while little is known about the physiological state of the striatum, the major input structure of the basal ganglia. In the present study, we recorded spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, mEPSCs, sIPSCs, mIPSCs) from projection neurons of the striatum of experimental HB. We found a selective reduction of striatal sEPSC and mEPSC frequency following chemical lesion of the STN of the rat, suggesting that reduced synaptic excitation of the input structure of the basal ganglia represents a physiological correlate of HB.

Anesthetics, Local↗

PubMed2006

Direct limits on the oscillation frequency.

We report results of a study of the B(s)(0) oscillation frequency using a large sample of B(s)(0) semileptonic decays corresponding to approximately 1 fb(-1) of integrated luminosity collected by the D0 experiment at the Fermilab Tevatron Collider in 2002-2006. The amplitude method gives a lower limit on the B(s)(0) oscillation frequency at 14.8 ps(-1) at the 95% C.L. At delta m(s) = 19 ps(-1), the amplitude deviates from the hypothesis A= 0(1) by 2.5 (1.6) standard deviations, corresponding to a two-sided C.L. of 1% (10%). A likelihood scan over the oscillation frequency, delta m(s), gives a most probable value of 19 ps(-1) and a range of 17 < delta m(s) < 21 ps(-1)at the 90% C.L., assuming Gaussian uncertainties. This is the first direct two-sided bound measured by a single experiment. If delta m(s) lies above 22 ps(-1), then the probability that it would produce a likelihood minimum similar to the one observed in the interval 16-22 ps(-1) is (5.0 +/- 0.3)%.

Journal Article↗

PubMed2006

Oligodendrocytes express P2Y12 metabotropic receptor in adult rat brain.

In the CNS, nucleotide receptors termed P2 receptors are identified on neurons and glial cells, mediating neuron-neuron, glia-glia and glia-neuron communication. In the present work, we qualify in vivo in the adult rat CNS the cellular/subcellular distribution of P2Y12 receptor protein in cerebral cortex, white matter and subcortical nuclei (striatum and substantia nigra), by means of immunofluorescence-confocal, electron microscopy and Western blot analysis. P2Y12 receptor immunoreactivity colocalizes neither with markers such as neuronal nuclei, neurofilament light chain, calbindin and tyrosine hydroxylase, nor with glial fibrillary acidic protein and isolectin B4, but with myelin basic protein and the oligodendrocyte marker RIP, in both cell bodies and processes, indicating therefore oligodendrocyte localization. Electron microscopy identifies P2Y12 receptors in both the perikaryon and under the plasmalemma of oligodendrocyte cell bodies and radiating processes, until the paranodal region of fibers. By Western blot analysis, P2Y12 receptor shows a specific band of 42-44 kDa, matching the molecular mass predicted from amino acid sequencing. Since in platelets P2Y12 receptor is known to regulate adhesion/activation and thrombus growth/stability, from our results we could speculate by analogy that, in oligodendrocytes, P2Y12 receptor signaling might contribute to the migration and adhesion of the glial processes to axons to be myelinated.

Animals↗

PubMed2006

Distinct roles for spinophilin and neurabin in dopamine-mediated plasticity.

Protein phosphatase 1 plays a major role in the governance of excitatory synaptic activity, and is subject to control via the neuromodulatory actions of dopamine. Mechanisms involved in regulating protein phosphatase 1 activity include interactions with the structurally related cytoskeletal elements spinophilin and neurabin, synaptic scaffolding proteins that are highly enriched in dendritic spines. The requirement for these proteins in dopamine-related neuromodulation was tested using knockout mice. Dopamine D1-mediated regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor activity was deficient in both striatal and prefrontal cortical neurons from neurabin knockout mice; in spinophilin knockout mice this deficit was manifest only in striatal neurons. At corticostriatal synapses long-term potentiation was deficient in neurabin knockout mice, but not in spinophilin knockout mice, and was rescued by a D1 receptor agonist. In contrast, long-term depression was deficient in spinophilin knockout mice but not in neurabin knockout mice, and was rescued by D2 receptor activation. Spontaneous excitatory post-synaptic current frequency was increased in neurabin knockout mice, but not in spinophilin knockout mice, and this effect was normalized by D2 receptor agonist application. Both knockout strains displayed increased induction of GluR1 Ser(845) phosphorylation in response to D1 receptor stimulation in slices, and also displayed enhanced locomotor activation in response to cocaine administration. These effects could be dissociated from cocaine reward, which was enhanced only in spinophilin knockout mice, and was accompanied by increased immediate early gene induction. These data establish a requirement for synaptic scaffolding in dopamine-mediated responses, and further indicate that spinophilin and neurabin play distinct roles in dopaminergic signal transduction and psychostimulant response.

Animals↗

PubMed2006

Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations.

OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. METHODS: In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. RESULTS: Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. CONCLUSIONS: These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics.

Aged↗

PubMed2006

Striatal metabotropic glutamate receptors as a target for pharmacotherapy in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc). The symptoms are resting tremor, slowness of movement, rigidity and postural instability. Evidence that an imbalance between dopaminergic and cholinergic transmission takes place within the striatum led to the utilization of DA precursors, DA receptor agonists and anticholinergic drugs in the symptomatic therapy of PD. However, upon disease progression the therapy becomes less effective and debilitating effects such as dyskinesias and motor fluctuations appear. Hence, the need for the development of alternative therapeutic strategies has emerged. Several observations in different experimental models of PD suggest that blockade of excitatory amino acid transmission exerts antiparkinsonian effects. In particular, recent studies have focused on metabotropic glutamate receptors (mGluRs). Drugs acting on group I and II mGluRs have indeed been proven useful in ameliorating the parkinsonian symptoms in animal models of PD and therefore might represent promising therapeutic targets. This beneficial effect could be due to the reduction of both glutamatergic and cholinergic transmission. A novel target for drugs acting on mGluRs in PD therapy might be represented by striatal cholinergic interneurons. Indeed, the activation of mGluR2, highly expressed on this cell type, is able to reduce calcium-dependent plateau potentials by interfering with somato-dendritic N-type calcium channel activity, in turn reducing ACh release in the striatum. Similarly, the blockade of both group I mGluR subtypes reduces cholinergic interneuron excitability, and decreases striatal ACh release. Thus, targeting mGluRs located onto cholinergic interneurons might result in a beneficial pharmacological effect in the parkinsonian state.

Animals↗

PubMed2006

Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase.

DJ-1 gene mutations lead to an inherited form of early-onset parkinsonism. The function of DJ-1 is unclear, though a neuroprotective role has been postulated. Electrophysiological recordings were made of striatal and dopaminergic nigral neurons both of wild-type (WT) and DJ-1-knockout (DJ-1(-/-)) mice. We assessed the responses of dopaminergic cells to combined oxygen and glucose deprivation (OGD), and to the mitochondrial toxin rotenone. OGD induced a membrane hyperpolarization in nigral neurons from WT mice. Similarly, rotenone hyperpolarized neurons and then a depolarization occurred. In DJ-1(-/-) mice, the OGD-induced hyperpolarization was significantly enhanced. Moreover, rotenone caused a shorter hyperpolarization followed by an irreversible depolarization. To evaluate the involvement of Na+/K+ ATPase, we tested ouabain, a Na+/K+ ATPase inhibitor, on two distinct neuronal subtypes. Compared to WT mice, in dopaminergic neurons from DJ-1(-/-) mice, ouabain induced rapid and irreversible membrane potential changes. Notably, this effect was observed at concentrations that were unable to produce membrane potential shifts on striatal spiny neurons, both from WT and DJ-1(-/-) mice. These findings suggest that DJ-1 loss-of-function enhances vulnerability to energy metabolism alterations, and that nigral neurons are particularly sensitive to Na+/K+ ATPase impairment.

Animals↗

PubMed2006

A study to validate the method based on DIMOND quality criteria for cardiac angiographic images.

A method based on image quality criteria (QC) for cine-angiography was developed to measure the quality of cine-angiograms (CA). A series of 30 CA for left ventriculography (LV) and left and right coronary angiography (LCA, RCA) have been scored and 172 readings were obtained. Standard deviation of quality scores indicated the reproducibility of the method. Each part of CA was examined separately, giving scores for LV, LCA and RCA and a total score (TS), with clinical (C) and technical (T) criteria defined and examined separately. In 83% of the studies TS was >0.8 and with standard deviation from 0.02 to 0.21. In general, LV had a lower score and greater disagreement compared with RCA and LCA. Disagreement was greater in T, compared with C. In conclusion, these results indicate that QC, translated into a scoring system, yields reproducible data on the quality of cardiac images.

Cineangiography↗

PubMed2006

Reference levels in PTCA as a function of procedure complexity.

The multicentre assessment of a procedure complexity index (CI) for the introduction of reference levels (RLs) in percutaneous transluminal coronary angioplasties (PTCA) is presented here. PTCAs were investigated based on methodology proposed by Bernardi et al. Multiple linear stepwise regression analysis, including clinical, anatomical and technical factors, was performed to obtain fluoroscopy time predictors. Based on these regression coefficients, a scoring system was defined and CI obtained. CI was used to classify dose values into three groups: low, medium and high complexity procedures, since there was good correlation (r = 0.41; P < 0.001) between dose-area product (DAP) and CI. CI groups were determined by an ANOVA test, and the resulting DAP and fluoroscopy time third quartiles suggested as preliminary RLs in PTCA, as a function of procedure complexity. PTCA preliminary RLs for DAP are 54, 76 and 127 Gy cm2, and 12, 20 and 27 min for fluoroscopy time, for the three CI groups.

Analysis of Variance↗

PubMed2006

On the use of DICOM cine header information for optimisation: results from the 2002 European DIMOND cardiology survey.

The paper explores the level of information contained within the DICOM header in images from various cardiology systems. Data were obtained in the European DIMOND survey on image quality (Italy, Ireland, Belgium, Greece and Spain). Images from five standard diagnostic cardiology procedures carried out in six European hospitals have been analysed. DICOM header information was extracted to a database in order to analyse how it could help in the optimisation of the procedures. The level of data contained in the headers differs widely between cardiology systems. None of the X-ray systems in the 2002 survey archives the dosimetric data in the DICOM header. The mean number of runs per procedure ranges between 7.5 and 15.4 and the mean number of frames per procedure between 575 and 1417. Differences in kVp, mA, pulse time, distances and C-arm angulations are substantial and suggest that there exists a wide range for optimisation.

Cardiology↗